Differential Gene Expression Profiles of Pancreatic Ductal Adenocarcinomas Among African American and Caucasian American Patients
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ABSTRACT:
PROVIDER: PRJNA1246143 | ENA |
REPOSITORIES: ENA
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Project description:PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths. In the United States (US), African Americans (AA) have higher PDAC incidence and mortality than Caucasian Americans (CA). This study aimed to identify distinct gene expression patterns and differentially regulated pathways in AA and CA PDACs. METHODS: Whole transcriptomic analyses were conducted on FFPE sections of PDACs (n=40) from AA (9 PDAC/3 normal) and CA (31 PDAC/5 normal) tissues to evaluate differential expression and signaling pathways within and between racial groups and to identify distinctive and common genes/pathways. RESULTS: We identified uniquely upregulated genes in both racial groups. Among the 25 top upregulated genes in AA PDACs, compared to their normal tissues, were CHST15, PARP15, and NUDT16. Altered pathways in AA PDACs included glycerophospholipid metabolism and regulation of lipolysis in adipocytes. In contrast, a different set of top 25 upregulated genes was found in CA PDACs, including SERPINB3, PADI1, H3C8, and ZNF488. The altered pathways in CA PDACs included cellular senescence and PD−L1/PD−1 checkpoint pathways. Thirteen genes (seven upregulated and six downregulated) were differentially modulated in AA vs. CA PDACs. Using a publicly available database, we analyzed the top 25 upregulated genes (normal vs. tumor) and seven differentially upregulated genes (AA vs. CA) for associations with survival outcomes. Eight genes (CHST15, PARP15, NUDT16, SERPINB3, PADI1, H3C8, ZNF488, and LETM2) correlated with poor survival. CONCLUSION: These findings show distinct gene expression profiles and modulated pathways in AA and CA PDACs, supporting development of race-based therapeutic targets.
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Project description:Triple negative breast cancer is an aggressive phenotypic breast cancer characterized by ER negative, PR negative and Her2 negative immunohistochemistry status. We embarked on a study to explore the transcriptome of African American and Caucasian TNBC patients and identify race specific biomarkers.
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Project description:RATIONALE: Gathering information about timely diagnosis in African American and Caucasian patients with newly diagnosed colorectal cancer may help doctors learn more about factors that influence a diagnosis and plan the best treatment.
PURPOSE: This phase I trial is studying differences in timely cancer diagnosis in African American patients and in Caucasian patients with newly diagnosed colorectal cancer.
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Project description:There is drastic racial disparities between Caucasian (CA) and African American (AA) for breast cancer. Circulating microRNAs exhibit stability and may serve as biomarkers in clinical settings. To discover potential microRNAs that mediate intercellular crosstalk and as biomarkers underlying the breast cancer racial disparity, serum exosomes from CA and AA were extracted and analyzed for its microRNA contents using small RNA sequencing.
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Project description:To determine whether optic nerve head astrocytes, a key cellular component of glaucomatous neuropathy, exhibit differential gene expression in primary culture of astrocytes from African American donors with or without glaucoma, compared to astrocytes from Caucasian American donors with or without glaucoma. Experiment Overall Design: We divided samples into four group: Caucasian American normal, Caucasian American with glaucoma, African American normal and African American with glaucoma. We analyzed data from Affymetrix Human Genome U133A 2.0 and U95 chips.
2008-04-07 | E-GEOD-9944 | biostudies-arrayexpress
Project description:To determine whether optic nerve head astrocytes, a key cellular component of glaucomatous neuropathy, exhibit differential gene expression in primary culture of astrocytes from normal African American donors, compared to astrocytes from normal Caucasian American donors. All donors have no histories of eye disease, diabetes, or chronic CNS disease. Experiment Overall Design: We divided samples into two groups: normal Caucasian American and normal African American. We analyzed data from Affymetrix Human Genome Human Genome U133A and U133A 2.0 chips.
2008-06-17 | E-GEOD-9939 | biostudies-arrayexpress
Project description:To determine whether optic nerve head astrocytes, a key cellular component of glaucomatous neuropathy, exhibit differential gene expression in primary culture of astrocytes from normal African American donors, compared to astrocytes from normal Caucasian American donors. All donors have no histories of eye disease, diabetes, or chronic CNS disease. Keywords: Gene expression profile
2008-01-31 | GSE9939 | GEO
Project description:To determine whether optic nerve head astrocytes, a key cellular component of glaucomatous neuropathy, exhibit differential gene expression in primary culture of astrocytes from African American donors with or without glaucoma, compared to astrocytes from Caucasian American donors with or without glaucoma. Keywords: Gene expression profile
2008-01-31 | GSE9944 | GEO
Project description:Transcriptional profiling of human T cells analyzing the impact of race on the responsiveness to IFNa in healthy blood donors. Control and IFNa-treated samples derived from healthy Caucasian American vs. African American blood donors are compared.
2010-01-27 | GSE17952 | GEO
Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Experiment Overall Design: A total of 69 fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens (n = 59) were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the specimens. These tissues were collected between 2002 and 2004 at four different sites, with each site providing tissues from both African-American and European-American patients. Information on race/ethnicity (33 African-Americans and 36 European-Americans) was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire in which race/ethnicity was self-reported (UMD). Only one patient, a European-American, was also Hispanic. Surrounding non-tumor prostate tissue was collected from 18 of the recruited patients in this study. Of those, 7 were African-American men and 11 were European-American men. We also isolated total RNA from 10 needle biopsy specimens collected from patients at the National Naval Medical Center (one African-American and 9 European-Americans) that did not have prostate cancer. From those, we prepared two RNA pools, each representing 5 patients. Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. Written informed consent was obtained from all donors. Tissue collection and study design were approved by the institutional review boards of the participating institutions.
2008-06-15 | E-GEOD-6956 | biostudies-arrayexpress